Unstimulated cortisol secretory activity in everyday life and its relationship with fatigue and chronic fatigue syndrome: A systematic review and subset meta-analysis

Editor's Comment: The cortisol awakening response (CAR) is a 50% surge in cortisol levels that occurs roughly 30 minutes after waking. Because cortisol is released in response to stress, a reduced level of cortisol would indicate an impairment of the HPA (hypothalamus-pituitary-adrenal) - axis, and a subsequent inability to adjust to stressors.

The hypothalamic–pituitary–adrenal (HPA) axis is a psychoneuroendocrine regulator of the stress response and immune system, and dysfunctions have been associated with outcomes in several physical health conditions. Its end product, cortisol, is relevant to fatigue due to its role in energy metabolism.

The systematic review examined the relationship between different markers of unstimulated salivary cortisol activity in everyday life in chronic fatigue syndrome (CFS) and fatigue assessed in other clinical and general populations. Search terms for the review related to salivary cortisol assessments, everyday life contexts, and fatigue.

Meta-analyses revealed an attenuation of the CAR increase within CFS compared to controls (d = ?.34) but no statistically significant differences between groups for other markers. In the narrative review, total cortisol output (CAR or CP) was rarely associated with fatigue in any population; CAR increase and DCS were most relevant.

Outcomes reflecting within-day change in cortisol levels (CAR increase; DCS) may be the most relevant to fatigue experience, and future research in this area should report at least one such marker. Results should be considered with caution due to heterogeneity in one meta-analysis and the small number of studies.